The Pediatric Oncology Group (POG) is a multi-disciplinary, multi- institutional research community which collaborates to increase knowledge of and improve treatment for cancer and leukemia in children and adolescents. The Montreal Children's Hospital/McGill University (MCH), a founding member, requests funding for itself and its two affiliates, the Children's Hospital of Eastern Ontario (CHEO) and the University of Sherbrooke Medical Center (USMC) to continue to participate fully in administrative and scientific activities of the POG during the next 5 years. We expect to enroll a total of 70 patients a year on therapeutic protocols for childhood leukemias, lymphomas, solid tumors and brain tumors, with continued emphasis on Phase I and II studies of new agents and coordination or co-coordination of a minimum of 13 protocols. We expect to enroll 110 patients per year on non-therapeutic studies of cancer etiology, epidemiology, biology, psychologic impact and late effects of therapy with particular emphasis on the pharmacology and molecular pharmacology of methotrexate in acute lymphoblastic leukemia (ALL). We will comply with all requirements of the POG constitution, with MR regulations governing ethical conduct of clinical research and with OPRR and IRB requirements for informed consent and protection of subjects from research risks. In addition to an anticipated doubling of patient accruals since 5 years ago, our major contributions to POG research will include: confirmation that the extent of accumulation of methotrexate polyglutamates by lymphoblasts in B-progenitor cell ALL correlates with event-free survival (EFS) and characterization of the mechanisms regulating this metabolism (Whitehead); promotion of new agent drug development through New Agents and Pharmacology Committee leadership (Whitehead and Bernstein) and protocol coordination (Bernstein, Baruchel); introduction of stereotactic and fractionated stereotactic radiation therapy in brain tumors (Freeman); coordination of treatment protocols of newly-diagnosed and relapsed B-progenitor cell ALL (Abish, Bernstein); introduction of new agents and combinations in recurrent lymphoid disease as Sub-committee Chair, Lymphoid Relapse (Bernstein); chemotherapy and surgery of brain tumors (Baruchel, Ventureyra); and study of the biology, including p53 gene mutations, and treatment of HIV-related lymphomas (Baruchel, Whitehead).